16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors

Two new 16-nor limonoids, harperspinoids A and B (1 and 2), with a unique 7/5/5/6/5 ring system, have been isolated from the plant Harrisonia perforate together with a known one, Harperforin G (3). Their structures were elucidated by NMR spectroscopy, X-ray diffraction analysis and computational mod...

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Autores principales: Yan, Xiao-Hui, Yi, Ping, Cao, Pei, Yang, Shi-Ying, Fang, Xin, Zhang, Yu, Bin Wu, Leng, Ying, Di, Ying-Tong, Lv, Yang, Hao, Xiao-Jiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105127/
https://www.ncbi.nlm.nih.gov/pubmed/27833136
http://dx.doi.org/10.1038/srep36927
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author Yan, Xiao-Hui
Yi, Ping
Cao, Pei
Yang, Shi-Ying
Fang, Xin
Zhang, Yu
Bin Wu,
Leng, Ying
Di, Ying-Tong
Lv, Yang
Hao, Xiao-Jiang
author_facet Yan, Xiao-Hui
Yi, Ping
Cao, Pei
Yang, Shi-Ying
Fang, Xin
Zhang, Yu
Bin Wu,
Leng, Ying
Di, Ying-Tong
Lv, Yang
Hao, Xiao-Jiang
author_sort Yan, Xiao-Hui
collection PubMed
description Two new 16-nor limonoids, harperspinoids A and B (1 and 2), with a unique 7/5/5/6/5 ring system, have been isolated from the plant Harrisonia perforate together with a known one, Harperforin G (3). Their structures were elucidated by NMR spectroscopy, X-ray diffraction analysis and computational modelling. Compound 1 exists as polymorphic crystals. Conformations of 1 in solution were further discussed based on the computational results. These compounds exhibited notable inhibitory activity against the 11β-HSD1 enzyme. Compound 3 had potencies for the inhibition of human 11β-HSD1 with high selectivity against 11β-HSD2 (IC(50) 0.58 μM, SI > 174). Molecular docking and quantitative structure-activity relationship studies revealed a mixed regulatory mechanism.
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spelling pubmed-51051272016-11-17 16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors Yan, Xiao-Hui Yi, Ping Cao, Pei Yang, Shi-Ying Fang, Xin Zhang, Yu Bin Wu, Leng, Ying Di, Ying-Tong Lv, Yang Hao, Xiao-Jiang Sci Rep Article Two new 16-nor limonoids, harperspinoids A and B (1 and 2), with a unique 7/5/5/6/5 ring system, have been isolated from the plant Harrisonia perforate together with a known one, Harperforin G (3). Their structures were elucidated by NMR spectroscopy, X-ray diffraction analysis and computational modelling. Compound 1 exists as polymorphic crystals. Conformations of 1 in solution were further discussed based on the computational results. These compounds exhibited notable inhibitory activity against the 11β-HSD1 enzyme. Compound 3 had potencies for the inhibition of human 11β-HSD1 with high selectivity against 11β-HSD2 (IC(50) 0.58 μM, SI > 174). Molecular docking and quantitative structure-activity relationship studies revealed a mixed regulatory mechanism. Nature Publishing Group 2016-11-11 /pmc/articles/PMC5105127/ /pubmed/27833136 http://dx.doi.org/10.1038/srep36927 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Yan, Xiao-Hui
Yi, Ping
Cao, Pei
Yang, Shi-Ying
Fang, Xin
Zhang, Yu
Bin Wu,
Leng, Ying
Di, Ying-Tong
Lv, Yang
Hao, Xiao-Jiang
16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors
title 16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors
title_full 16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors
title_fullStr 16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors
title_full_unstemmed 16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors
title_short 16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors
title_sort 16-nor limonoids from harrisonia perforata as promising selective 11β-hsd1 inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105127/
https://www.ncbi.nlm.nih.gov/pubmed/27833136
http://dx.doi.org/10.1038/srep36927
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